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Human Stem Cell and Organoid Models to Advance Acute Kidney Injury Diagnostics and Therapeutics
Authors:Naomi Pode-Shakked  Prasad Devarajan
Affiliation:1.Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel;2.Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Abstract:Acute kidney injury (AKI) is an increasingly common problem afflicting all ages, occurring in over 20% of non-critically ill hospitalized patients and >30% of children and >50% of adults in critical care units. AKI is associated with serious short-term and long-term consequences, and current therapeutic options are unsatisfactory. Large gaps remain in our understanding of human AKI pathobiology, which have hindered the discovery of novel diagnostics and therapeutics. Although animal models of AKI have been extensively studied, these differ significantly from human AKI in terms of molecular and cellular responses. In addition, animal models suffer from interspecies differences, high costs and ethical considerations. Static two-dimensional cell culture models of AKI also have limited utility since they have focused almost exclusively on hypoxic or cytotoxic injury to proximal tubules alone. An optimal AKI model would encompass several of the diverse specific cell types in the kidney that could be targets of injury. Second, it would resemble the human physiological milieu as closely as possible. Third, it would yield sensitive and measurable readouts that are directly applicable to the human condition. In this regard, the past two decades have seen a dramatic shift towards newer personalized human-based models to study human AKI. In this review, we provide recent developments using human stem cells, organoids, and in silico approaches to advance personalized AKI diagnostics and therapeutics.
Keywords:acute kidney injury   kidney organoids   kidney development   tubuloids
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